Calcium salt of a benzylsuccinic acid derivative (chemical name: (2S)-2-benzyl-3-(cis-hexahydro-2-iso-indolinylcarbonyl)propionic acid) represented by the formula:
or its hydrate, which is an active ingredient in the pharmaceutical composition of the present invention, has a remarkable lowering action of blood sugar and has been known as a compound useful as an agent for the treatment of diabetes (Japanese Patent Laid-Open No. 356459/1992).
Sulfonylurea agents (SU agents) such as glibenclamide, gliclazide and the like which have been frequently used for the treatment of diabetes take long to exert their effects and have persisting effects for several hours, so that it has been pointed out a problem that a risk of hypoglycemic symptoms increases conversely. For example, when SU agent is taken at a dose of sufficiently suppressing postprandial hyperglycemia, a problem that hypoglycemia is caused between meals can not be avoided. However, since effects of the present compound are shortly persistent, it is expected as a therapeutic agent for hyperglycemia which corrects only postprandial hyperglycemic condition without causing hypoglycemic condition between meals.
Rapid absorption after taking a drug in addition to early excretion of an active component from blood is required to correct only postprandial hyperglycemic condition without causing hypoglycemic condition between meals. Thus, development of immediate release preparations is needed in postprandial hyperglycemia treatment, wherein disintegration of the pharmaceutical composition and dissolution of the active ingredient are excellent. Generally, it is necessary for immediate release preparations to usually have an ability of about 75% or more drug release (drug dissolution) within 20 minutes after taking the drug (Iyakuhin no Kaihatsu [Development of medicines] Vol.11, pp.65–77, published by Hirokawa Shoten). It is concerned that the present compound is problematic in dissolution since it is poorly soluble in water. Therefore, in order to solve the problem, early development of excellent immediate release preparations has been greatly desired.